Globally it is estimated that there are about 280 million people with type-2 diabetes. The incidence varies substantially in different parts of the world, almost certainly because of genetic, nutritional, environmental and lifestyle factors. In the USA, roughly 21 million patients are diagnosed as having diabetes, 90% of whom are type-2, with a further 8.1 million people estimated to be undiagnosed diabetes sufferers. Diabetes is the 7th leading cause of death in the USA. The total cost of diabetes in the United States was $245 billion in 2012. Traditionally considered a disease of adults, type-2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates due to alterations in dietary patterns as well as in life styles during childhood.
The primary early development of diabetes may appear when insulin response to a meal, or more specifically first-phase insulin release, becomes abnormal (Gerich J E, 2002, Diabetes, 51:S117-S121) and elevated blood glucose becomes unavoidable over time. Then chronic hyperglycemia generates an increased insulin demand and eventually a beta-cell secretory dysfunction causing exhaustion of the beta-cells in the pancreas (Porte D J, 2001, Diabetes Metab Res Rev, 17(3):181-188). This dysfunction of the insulin secretion is believed to appear in parallel to a defect of the hepatic and peripheral insulin action, identified as the insulin resistance which induces elevated fasting blood insulin. Enhanced insulin secretion and insulin resistance both co-operate to increase insulinemia and favour the development of type-2 diabetes. As a consequence, a diminished and adequate response of the insulinemia after a meal could be the sign of an adequate insulin secretion and utilization by the body in healthy or pre-diabetic subjects. This decreased postprandial insulinemia should preserve the pancreatic function and simultaneously improve insulin sensitivity. In the long term, lowering the insulin demand after a meal can reduce (1) the risk of developing type-2 diabetes in pre-diabetic subjects and (2) the deterioration of the glycemic control in type-2 diabetes.
Proteins are known to stimulate insulin secretion and a high protein diet has the potential to lower plasma glucose and fasting triglycerides in type-2 diabetic subjects [Van Loon L J et al., 2000, Am J Clin Nutr 72:96-105; Gannon M C et al., 2003, Am J Clin Nutr 78:734-741]. A recent study evaluated the acute effects of different protein types on postprandial lipemia after a fat-rich test meal in type-2 diabetic subjects [Mortensen L S et al., 2009, Am J Clin Nutr. 90:41-48]. Thereby, 4 iso-caloric meals with different protein sources, i.e. whey, casein, gluten and cod protein, were compared. It was concluded that whey proteins were most effective in reducing postprandial lipemia in those patients. A further study published by Shertzer H G et al. [2011, J Nutr 141:582-587] revealed that dietary whey protein isolates administered to mice reduced the risk for metabolic disease and of developing diabetes associated with the consumption of a high-fat diet.
WO2011/112695 discloses that health benefits provided by whey proteins include control of blood glucose such that they are suitable for diabetics. WO2013/057232 discloses that whey protein micelles may be used in the treatment or prevention of a disorder linked to an increase in plasma postprandial insulin in a subject.
There is a persisting need in the food industry to further improve the nutritional solutions provided to diabetic subjects, subjects at risk for developing diabetes and subjects with impaired glucose metabolism.
The object of the present invention is to improve the state of the art and to provide a new and better nutritional solution for improving the postprandial insulin profile in a subject, particularly in a diabetic or pre-diabetic subject.
The object of the present invention is achieved by the subject matter of the independent claims. The dependent claims further develop the idea of the present invention.
Accordingly, the present invention provides in a first aspect a composition comprising polysaccharides and whey protein micelles for use in the treatment or prevention of a disorder linked to an increase in plasma postprandial insulin in a subject wherein the polysaccharides have a negative zeta potential at a pH value in the range 2.5 to 4.5 and the weight ratio of whey protein micelles to polysaccharides is between 30:1 and 0.8:1.
In a further aspect, the invention pertains to a non-therapeutic use of a composition comprising polysaccharides and whey protein micelles to decrease plasma postprandial insulin concentration, wherein the polysaccharides have a negative zeta potential at a pH value in the range 2.5 to 4.5 and the weight ratio of whey protein micelles to polysaccharides is between 30:1 and 0.8:1.
In a still further aspect, the present invention pertains to a process for forming polysaccharide-whey protein micelle complexes comprising the steps of, (a) combining a polysaccharide with an aqueous dispersion of whey protein micelles to form a composition comprising an aqueous dispersion of polysaccharide and whey protein micelles, wherein the polysaccharide has a negative zeta potential at a pH value in the range 2.5 to 4.5 and the weight ratio of whey protein micelles to polysaccharide is between 30:1 and 0.8:1 (b) if the pH of the composition comprising an aqueous dispersion of polysaccharide and whey protein micelles is not already between 2.5 and 4.5, then adjusting the pH of the composition to between 2.5 and 4.5 to form polysaccharide-whey protein micelle complexes.
“Whey protein micelles” are defined herein as described in EP1839492A1. Particularly, the “whey protein micelles” are the micelles comprised in the whey protein micelles concentrate obtainable by the process as disclosed in EP1839492A1. Therein, the process for the production of whey protein micelles concentrate comprises the steps of: a) adjusting the pH of a whey protein aqueous solution to a value between 3.0 and 8.0; b) subjecting the aqueous solution to a temperature between 80 and 98° C.; and c) concentrating the dispersion obtained in step b). Thereby, the micelles produced have an extremely sharp size distribution, such that more than 80% of the micelles produced have a size smaller than 1 micron in diameter and preferably are between 100 nm and 900 nm in size. The “whey protein micelles” can be in liquid concentrate or in powder form. Importantly, the basic micelle structure of the whey proteins is conserved, in the concentrate, the powder and reconstituted from the powder for example in water. The “whey protein micelles” are physically stable in dispersion, as powder as well as during spray-drying or freeze-drying.
“Insulin” is a hormone secreted by the beta cells of the pancreas in response to a meal. Insulin is central to regulating carbohydrate and fat metabolism in the body.
A high insulinogenic nutrition represents a chronic stimulus to the beta cells that may induce an adaptive hypertrophy and a progressive dysregulation of the cells, resulting in postprandial hyperinsulinemia. Postprandial hyperinsulinemia may promote weight gain, fat deposition and the development of insulin resistance, metabolic syndrome, glucose intolerance and type-2 diabetes (Kopp W., Metabolism. 2003, July; 52(7):840-844).